A Cohort Study of Incretin-based Therapy Combined With Insulin in Type 2 Diabetic Patients for 5 Years

This study is not yet open for participant recruitment.
Verified September 2012 by Nagaoka Red Cross Hospital
Sponsor:
Information provided by (Responsible Party):
Kyuzi Kamoi, Nagaoka Red Cross Hospital
ClinicalTrials.gov Identifier:
NCT01681550
First received: September 2, 2012
Last updated: September 8, 2012
Last verified: September 2012
  Purpose

The use of dipeptidyl-peptidase 4 (DPP-4) inhibitors and glucagon like peptide 1 (GLP1) analogues for the treatment of diabetic mellitus (DM) type 2 is growing (1,2). Currently, some of these agents have been approved in combination with insulin. The potential for combined use with insulin has garnered increasing attention due to reduce side effects associated with insulin therapy and improve glycemic control. Some investigators reported that GLP-1 analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction (3). However, their duration of treatment was short time with less than a mean of 3.0 years and the alterations of chronic diabetic complications by combination with incretin-based and insulin therapies are not known.

We evaluated the long effects of adding incretin-based therapy (DPP-4 inhibitors or GLP-1 analogues) to insulin therapy on glycated hemoglobin (HbA1c) as glycemic control, body mass index (BMI), blood pressure (BP), insulin dosage, frequency of hypoglycemia, and chronic diabetic complications for 5 years-treatments.


Condition Intervention
Type 2 Diabetes Mellitus
Drug: Incretin-based therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Incretin-based Therapy Combined With Insulin on HbA1c, Hypoglycemia and Chronic Diabetic Complications in Type 2 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Nagaoka Red Cross Hospital:

Primary Outcome Measures:
  • Death [ Time Frame: Duration varied between individual patients and was as the period of time after treatment with incretin-based therapy combined with insulin. ] [ Designated as safety issue: Yes ]
    The cause of death was determined by attending doctor or was assessed by interviewing the family.


Secondary Outcome Measures:
  • HbA1c [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    Duration varied between individual patients and was as the period of time until after treatment with incretin-based therapy combined with insulin.

  • BMI [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    BMI was calculated from body weight and height for at baseline and every 3 to 6 months throughout the study.

  • Blood pressure [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    Participants were examined using the same methods reported previously (4). Briefly, BP was measured in the clinic and at home on waking in the morning at trough by the same methods included device, device validation, observer, number of measurements, conditions, posture and cuffs described previously (4). Namely, clinic BP (CBP) was measured once in each clinic visit. Home BP (HBP) was measured every day in the morning within 10 minutes after awakening in the sitting position.

  • Insulin dose [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.

  • Hypoglycemia [ Time Frame: Average time requires 5 yearsinsulin. ] [ Designated as safety issue: Yes ]
    Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.

  • Hypoglycemia [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    Hypoglycemia and the number of time per day were assessed by medical examination owing to interview.

  • Microvascular complications including renal anemia [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    They were assessment by the method mentioned above. As renal anemia, serum hemoglobin (Hb) was measured by cyanmet-hemoglobin method using commercial reagent.

  • Macrovasular complications [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
    They were confirmed by medical history, including contents of treatment. New or worsened (recurrent) events were defined based on clinical manifestations and treatment throughout the study.


Estimated Enrollment: 500
Study Start Date: October 2012
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Incretin theapy combined with insulin Drug: Incretin-based therapy

Detailed Description:

Patients were treated with diet, exercise, and/or oral conventional pharmacotherapy combined with insulin. Oral conventional pharmacotherapy consisted of α-glycosidase inhibitors (α-GI), sulfonylurea (SU), biguanide (BG), thiazolidinedione (TZD), or combinations of these agents. Insulin therapy consisted of subcutaneous injections of long-acting insulin analogues prior to sleep and bolus subcutaneous injections of rapid-acting insulin analogues in multiple daily injections, or subcutaneous injections of mixed insulin analogues twice a day. In spite of the treatments, when the physician in charge judged that their values of HbA1c were inappropriate, the physician added the pharmacotherapy combined the insulin to incretin-based therapy. 2.3.2. For ethical reasons, patients were treated with various anti-hypertensive, anti-diabetic, anti-dyslipidemia and/or anti-hypercoagulation agents during the course of the study by the patients' own doctors as a part of continuing standard medical care. As to the drugs that have been used for the treatment of other disorders and its complication since the time before the study, the content should not be changed during the study in principle unless the complication is cured. If any new complication occurs during the study period, an appropriate treatment is given by the judgment of investigator.

  Eligibility

Ages Eligible for Study:   20 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

After a detailed baseline examination, 500 Japanese subjects with type 2 diabetes were followed up for all-cause mortality and morbidity. All participants visited our clinic regularly. All patients were fully informed about the purposes and procedures for the study and provided oral consent at enrolment.

Exclusion Criteria:

Patients participating in other clinical study. Other than the above, patients judged inappropriate as the subjects of this study by the investigator.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681550

Contacts
Contact: Kyuzi Kamoi, MD +81-0258-28-3600 kkam-int@echigo.ne.jp

Locations
Japan
Nagaoka Red Cross Hospital Not yet recruiting
Nagaoka, Niigata, Japan, 940-2085
Contact: Kyuzi Kamoi, MD    -81-0256-28-3600    kkam-int@echigo.ne.jp   
Sponsors and Collaborators
Nagaoka Red Cross Hospital
Investigators
Principal Investigator: Kyuzi Kamoi, MD Nagaoka Red Cross Hospital
  More Information

No publications provided

Responsible Party: Kyuzi Kamoi, MD, Nagaoka Red Cross Hospital
ClinicalTrials.gov Identifier: NCT01681550     History of Changes
Other Study ID Numbers: 8-Kamoi
Study First Received: September 2, 2012
Last Updated: September 8, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetes Complications
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Incretins
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014